The Lost Promise of a Heart Drug

Published: December 11, 2006

The failure of torcetrapib does not ''throw into question'' the theory of raising HDL (''good'') cholesterol any more than previously. What the failure of this drug throws into question is the theory of raising HDL by a mechanism called CETP inhibition, the mechanism of torcetrapib and some other compounds in development.

It should be noted that the mechanism of CETP inhibition was always considered questionable. There are other drugs, both in present use and in development, that affect HDL function (with or without raising HDL cholesterol) by different mechanisms, and their potential for benefit is still very much alive and kicking.

Robert Tota, M.D.
Fairfield, Conn., Dec. 5, 2006

To the Editor:

Pfizer appears to have created the buzz for its new drug torcetrapib when early study results, published in 2004 in The New England Journal of Medicine, showed that it can sharply boost levels of good cholesterol and lower bad cholesterol. But these are only surrogate endpoints.

Perhaps many more deaths could be averted in the future if medical journals refused to publish heart-drug studies until they demonstrate meaningful endpoints, like a lower rate of heart attack, stroke and deaths.

It is regrettable when a promising drug must be withdrawn after enormous expense and effort. But diet and lifestyle modification, including physical activity, and use of complementary dietary approaches and dietary supplements, benefit patients with cardiovascular disease.

Research into these modalities has received minimal financing compared with drug trials.

In particular, the long-chain omega-3 fatty acids, EPA and DHA, have shown benefit in a wide range of cardiovascular and other health conditions.

Omega-3 fatty acids are proved to be safe, well tolerated, easily managed and free of significant side effects, yet they are not yet part of the standard of care.

It is important to continue to expand all options for reducing the incidence and severity of heart disease, including revisiting available solutions that are safe, inexpensive and underutilized.

The writers are, respectively, director of the Institute of Human Nutrition; and director of the Rosenthal Center for Complementary and Alternative Medicine, Columbia University College of Physicians and Surgeons.

To the Editor:

Your Dec. 4 front-page article about the demise of torcetrapib, Pfizer's experimental drug aimed at elevating HDL (''good'') cholesterol, left the impression that all medications that raise HDL could somehow be harmful.

Niacin (one of the B vitamins) and a class of drugs called fibrates safely and successfully increase HDL.

Both also lower levels of LDL (''bad'') cholesterol and triglycerides, the main type of fat circulating in the bloodstream.

Niacin and the fibrates have been around for decades. They aren't magic bullets against heart disease -- nothing is -- but large-scale clinical trials show that the use of either can reduce the chances of having a heart attack or dying of cardiovascular disease.

Patrick J. Skerrett
Editor, Harvard Heart Letter
Boston, Dec. 4, 2006

To the Editor:

Re ''Collapse of a Cholesterol Drug'' (editorial, Dec. 5):

Though the collapse of Pfizer's cholesterol drug torcetrapib was disheartening to thousands of heart patients, Pfizer should also be lauded for its quick response in terminating the drug trial and its willingness to heed science over profit.

In a world in which we hear so much criticism of drug makers for exorbitant prices and their willingness to put profits ahead of patients, it is refreshing that Pfizer acted responsibly and quickly, even knowing the devastating impact on its stock price and future profits that this announcement would have.

The makers of Vioxx, and really all the drug makers, could take a lesson.

Brandon Savage
Yuba City, Calif., Dec. 5, 2006

To the Editor:

Re ''Collapse of a Cholesterol Drug'':

You refer to ''me too'' drugs as offering ''a merely incremental advance over some existing therapy,'' but there is no reason to think that they offer any advance at all.

In the clinical trials required for approval by the Food and Drug Administration, manufacturers do not have to compare ''me too'' drugs with old drugs in the same class, only with placebos.

For all we know, then, each new ''me too'' drug may be worse than existing ones.

The answer is for Congress to authorize the F.D.A. to require new drugs to be compared head to head with old ones.

Marcia Angell, M.D.
Cambridge, Mass., Dec. 5, 2006

The writer, a senior lecturer in social medicine at Harvard Medical School, was an editor in chief of The New England Journal of Medicine.

To the Editor:

I was glad to see that your editorial recognizes the high financial risks taken by the pharmaceutical companies as they search out new lifesaving drugs.

Many previous editorials in your paper have chastised the companies for their drug pricing. Now the public can be aware of both sides of the profit-to-loss formula.

A. Joseph Dresner
Ann Arbor, Mich., Dec. 5, 2006

The writer is a former biostatistician for Parke Davis/Warner Lambert Research Center.